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https://www.readbyqxmd.com/read/28523586/ocrelizumab-first-global-approval
#1
James E Frampton
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS...
June 2017: Drugs
https://www.readbyqxmd.com/read/28522962/alterations-in-cd200-cd200r1-system-during-eae-already-manifest-at-presymptomatic-stages
#2
Tony Valente, Joan Serratosa, Unai Perpiñá, Josep Saura, Carme Solà
In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28515158/the-anti-psoriatic-drug-monomethylfumarate-increases-nuclear-factor-erythroid-2-related-factor-2-nrf2-levels-and-induces-aquaporin-3-aqp3-mrna-and-protein-expression
#3
Inas Helwa, Vivek Choudhary, Xunsheng Chen, Ismail Kaddour-Djebbar, Wendy B Bollag
BACKGROUND: Oxidative stress contributes to inflammatory skin diseases including psoriasis. Monomethylfumarate (MMF) is an anti-psoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular anti-oxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. OBJECTIVE: We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28513788/comparisons-of-iga-response-in-saliva-and-colostrum-against-oral-streptococci-species
#4
Barbara Bellocchio Bertoldo, Camilla Beatriz da Silva, Denise Bertulucci Rocha Rodrigues, Vinicius Rangel Geraldo-Martins, Virginia Paes Leme Ferriani, Ruchele Dias Nogueira
The present study compared IgA specificity against oral streptococci in colostrum and saliva samples. Sixty-two mother-and-child pairs were included; samples of colostrum (C) and saliva (MS) were collected from the mothers and saliva samples were collected from babies (BS). The specificity of IgA against Streptococcus mutans and S. mitis were analyzed by western blot. Only 30% of babies' samples presented IgA reactivity to S. mutans, while 74 and 80% of MS and C, respectively, presented this response. IgA reactivity to S...
May 15, 2017: Brazilian Oral Research
https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#5
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28511117/conditioned-medium-from-relapsing-remitting-multiple-sclerosis-patients-reduces-the-expression-and-release-of-inflammatory-cytokines-induced-by-lps-gingivalis-in-thp-1-and-mo3-13-cell-lines
#6
Patrizia Ballerini, Francesca Diomede, Nicola Petragnani, Simona Cicchitti, Ilaria Merciaro, Marcos F X B Cavalcanti, Oriana Trubiani
The present research was aimed at evaluating the effect of the conditioned medium (CM) from human periodontal ligament stem cells (hPDLSCs) obtained from healthy donors (hPDLSCs-CM) and from Relapsing-Remitting Multiple Sclerosis patients (RR-MS-CM) on inflammatory response induced by Porphyromonas gingivalis lipopolysaccharide (LPS-G) in a monocytoid human cell line (THP-1) and human oligodendrocyte cell line (MO3.13). Human periodontal ligament biopsies were carried out from control donor patients and selected RR-MS donors...
May 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28508977/thrombotic-microangiopathy-caused-by-interferon-%C3%AE-1b-for-multiple-sclerosis-a-case-report
#7
Haruomi Nishio, Tatsuo Tsukamoto, Takeshi Matsubara, Yoichiro Okada, Ryosuke Takahashi, Motoko Yanagita
A 41-year-old man with a history of multiple sclerosis (MS) developed thrombotic microangiopathy after taking interferon β-1b for 10 years. Although the relapse of his MS was well controlled under normal blood pressure, he had persistent nausea, anorexia, gait disturbance and visual disorder 1 month before admission. He showed lethargy and high blood pressure (180/102 mmHg). Laboratory test results revealed anemia and thrombocytopenia, elevated LDH and renal dysfunction. Urinary dipstick showed a 2+ result for proteinuria and 3+ for hematuria...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28506921/decrease-of-blood-anti-%C3%AE-1-3-galactose-abs-levels-in-multiple-sclerosis-ms-and-clinically-isolated-syndrome-cis-patients
#8
L Le Berre, J Rousse, P-A Gourraud, B-M Imbert-Marcille, A Salama, G Evanno, G Semana, A Nicot, E Dugast, P Guérif, C Adjaoud, T Freour, S Brouard, F Agbalika, R Marignier, D Brassat, D-A Laplaud, E Drouet, V Van Pesch, J-P Soulillou
The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals...
May 18, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28505965/determining-the-igm-and-igg-antibody-titer-against-cmv-and-helicobacter-pylori-in-the-serum-of-multiple-sclerosis-patients-comparing-to-the-control-group-in-hamadan
#9
Masome Afiati Salim, Mohammad Mahdi Eftekharian, Mohammad Taheri, Mohammad Yousef Alikhani
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that disables Central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an important role in the MS pathology. The infection with helicobacter pylori also is recognized as a protective agent against MS in female. METHODS: Serum samples were isolated and frozen at -70°C. The earlier mentioned anti-virus antibodies and antibacterial antibodies were quantified by Elisa kit. RESULTS: The results showed that IgG antibody average value against cytomegalovirus in the blood of multiple sclerosis patients not only decreased but also was significant statistically (p< 0...
May 5, 2017: Human Antibodies
https://www.readbyqxmd.com/read/28502906/anti-inflammatory-effects-of-forsythia-suspensa-in-dextran-sulfate-sodium-induced-colitis
#10
Youn-Hwan Hwang, Dong-Gun Kim, Wei Li, Hye Jin Yang, Nam-Hui Yim, Jin Yeul Ma
ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa Fructus (FS) is used to treat various inflammatory disorders in traditional Oriental medicine, including gastrointestinal diseases, but its therapeutic potential in ulcerative colitis is unclear. Thus, we investigated any potential therapeutic effects of FS against intestinal inflammation and the bioactive constituents in FS. MATERIALS AND METHODS: After the induction of colitis using 3% dextran sulfate sodium, FS (100mg/kg/day) was administered orally during the experimental period...
May 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28499934/matrine-promotes-oligodendrocyte-development-in-cns-autoimmunity-through-the-pi3k-akt-signaling-pathway
#11
Shuqing Liu, Mingliang Zhang, Huijun Zhang, Fangzhou Liu, Raojuan Chu, Guang-Xian Zhang, Lin Zhu
AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset...
May 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28494768/inhibition-of-cd40-traf6-interactions-by-the-small-molecule-inhibitor-6877002-reduces-neuroinflammation
#12
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Susanne M A van der Pol, Barbara Zarzycka, Priscilla D A M Heijnen, Linda Beckers, Myrthe den Toom, Marion J J Gijbels, Louis Boon, Christian Weber, Helga E de Vries, Gerry A F Nicolaes, Christine D Dijkstra, Gijs Kooij, Esther Lutgens
BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation...
May 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28473732/anti-inflammatory-and-neuroprotective-role-of-natural-product-securinine-in-activated-glial-cells-implications-for-parkinson-s-disease
#13
Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J Lithgow, Julie K Andersen, Shankar J Chinta
Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson's disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28470769/how-human-iggs-against-myelin-basic-protein-mbp-recognize-oligopeptides-and-mbp
#14
Sergey Belov, Valentina N Buneva, Georgy A Nevinsky
Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis...
May 4, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28466255/formyl-peptide-receptor-1-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#15
Kai Bihler, Eugenia Kress, Stefan Esser, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Lars-Ove Brandenburg
Multiple sclerosis (MS) is a chronic degenerative disease of the central nervous system that is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation. Unclear are the factors triggering gliosis and demyelination. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. The innate immune response is induced by pathogen-associated or danger-associated molecular patterns, which are identified by pattern recognition receptors (PRRs), including the G-protein coupled with formyl peptide receptors (FPRs)...
May 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28466012/obesity-induces-artery-specific-alterations-evaluation-of-vascular-function-and-inflammatory-and-smooth-muscle-phenotypic-markers
#16
Antonio Garcia Soares, Maria Helena Catelli de Carvalho, Eliana Akamine
Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM) phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA) and thoracic aorta (TA)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28463791/%C3%AE-caryophyllene-ameliorates-the-development-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#17
Lívia B A Fontes, Débora Dos S Dias, Beatriz J V Aarestrup, Fernando M Aarestrup, Ademar A Da Silva Filho, José Otávio do Amaral Corrêa
Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice...
April 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28461106/effector-and-regulatory-b-cells-in-multiple-sclerosis
#18
Elsebeth Staun-Ram, Ariel Miller
The role of B cells in the pathogenesis of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, is becoming eminent in recent years, but the specific contribution of the distinct B cell subsets remains to be elucidated. Several B cell subsets have shown regulatory, anti-inflammatory capacities in response to stimuli in vitro, as well as in the animal model of MS: Experimental Autoimmune Encephalomyelitis (EAE). However, the functional role of the B regulatory cells (Bregs) in vivo and specifically in the human disease is yet to be clarified...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28457906/widespread-cortical-demyelination-of-both-hemispheres-can-be-induced-by-injection-of-pro-inflammatory-cytokines-via-an-implanted-catheter-in-the-cortex-of-mog-immunized-rats
#19
Muammer Üçal, Michaela Tanja Haindl, Milena Z Adzemovic, Johannes Strasser, Lisa Theisl, Manuel Zeitelhofer, Klaus Kraitsy, Stefan Ropele, Ute Schäfer, Franz Fazekas, Sonja Hochmeister
Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats...
April 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28452565/administration-of-wasabia-koreana-ameliorates-irritable-bowel-syndrome-like-symptoms-in-a-zymosan-induced-mouse-model
#20
Bo-Kyung Park, Eunho Chun, Jeong June Choi, Younmin Shin, Young Tak Kho, Seung Hyun Oh, Sun Yeou Kim, Taek Hwan Lee, Tae-Wan Kim, Eunju Shin, Seon-Gil Do, Mirim Jin
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with complex pathophysiology involving the brain-gut axis. To assess the effects of Wasabia koreana (WK) on IBS, we employed a mouse model of colonic zymosan injection presenting with diarrhea-predominant IBS-like symptoms. Oral WK administration significantly diminished stool score, suppressed colon length and weight change, and minimized body weight loss without affecting food intake. In WK-treated mice, the submucosal thickening and epithelial lining of the colon were inhibited and were similar to those of naïve mice...
May 2017: Journal of Medicinal Food
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